Table 2.
Correlations between GI transit and symptoms in IBS during controlled treatment interventions
| Drug | Dose | IBS study subjects | Study design | Transit methodology | Effect on GI transit vs placebo (or no drug) in IBS | Effect on IBS symptoms |
|---|---|---|---|---|---|---|
| Bulking agents | ||||||
| Bran97 | 15 g × 3 days | 12 “Bloated” IBS (10 F, 2 M) | DB, PC, crossover | Scintigraphy | Accelerated overall transit | NR |
| Calcium polycarbophil98 | 3 g/day × 8 weeks | 26 IBS (14 IBS-D and 12 IBS-C, 19F, 7 M) | Open-labelled study (drug vs baseline) | Radio-opaque markers | Prolonged CT time in IBS-D and reduced CT time in IBS-C compared with baseline | CT time negatively correlated with stool form (Bristol scale, r = −0.60) and stool frequency (r = −0.56) but not abdominal pain (r = −0.18) |
| Antispasmodic agents | ||||||
| Pinaverium bromide99 | 10 mg po tid × 2 weeks | 43 IBS (38F, 5M) | PC crossover | Radio-opaque markers | NS | NR |
| Cimetropium bromide100 | 50 mg tid × 4 weeks | 40 IBS (25 IBS-C, 15 IBS-D, 24 F, 16 M) | DB, PC, parallel group design | Radio-opaque markers | Accelerated CT in those with prolonged transit times; no effect in IBS with shorter transit times | NR |
| Tricylic antidepressants | ||||||
| Imipraine82 | 50 mg po qhs and increased to 100 po qhs × 5 days | 6 IBS-D (3 F, 3 M) | Open-labelled study (drug ≥3 weeks vs baseline) | Lactulose hydrogen breath test | Increase in orocaecal transit time | NR |
| Cholecystokinin-1 antagonist | ||||||
| Dexloxiglumide101 | 200 mg po tid × 7–9 days | 36 IBS-C (all F) | DB, randomised, parallel group design | Scintigraphy | Accelerated GE and slowed ascending colon emptying but no effect on overall CT | CT time positively correlated with composite score of bowel function (r = 0.43), but no effect on IBS symptoms |
| Serotonergic agents | ||||||
| Alosetron (5-HT3 antagonist)102 | 2 mg po bid × 8 days | 13 non-constipated IBS (9 F, 4 M) | DB, PC crossover | Radio-opaque markers and breath hydrogen test | Slowed proximal colon transit but no effect on orocaecal or left colon transit | NR |
| Alosetron (5-HT3 antagonist)53 | 1 mg bid or 4 mg bid | 25 non-constipated IBS | DB, PC, 2 dose study (n = 10 in each drug group and n = 5 in placebo group) | Scintigraphy | No significant change in GE, small intestinal transit time or CT time | NR |
| Alosetron (5-HT3 antagonist)103 | 1 mg bid × 6 weeks | 30 IBS-D (15 F, 15M) | Open-labelled study (drug vs baseline) | Scintigraphy | Slowed orocaecal transit (but not GE) and CT compared with baseline Trend for greater slowing in CT in F vs. M |
NR |
| Ondansetron (5-HT3 antagonist)55 | 16 mg tid × 4 weeks with 4 week washout between treatment periods | 14 IBS-D (6 F, 8 M) | DB, PC crossover study | Breath hydrogen test and radio-opaque markers | No effect on orocaecal or small intestinal transit times; no significant effect on CT | NR |
| Tegaserod (5-HT4 agonist)104 | 2 mg po bid × 1 week | 24 IBS-C (all F) | DB, PC, parallel group study | Scintigraphy | Accelerated proximal colon emptying but no effect on GE or overall CT | NR |
| Renzapride (5-HT4 agonist/5-HT3 antagonist)105 | 1, 2 or 4 mg/day × 11–14 days | 48 IBS-C (46 F, 2M) | DB, PC, dose-ranging, parallel group (n = 12/group) | Scintigraphy | No significant effect on GE and small intestinal transit, but significant linear dose response for CT to renzapride and for 4 mg dose vs placebo | Acceleration of CT positively correlated with improvements in ease of passage (r = 0.54) and stool form (r = 0.59) but not stool frequency |
| Renzapride (5-HT4 agonist/5-HT3 antagonist)106 | Placebo × 4 weeks, then 2 mg qd × 4 weeks and increasing to 2 mg bid × 4 weeks | 20 IBS-C (12 F, 8 M) | SB, PC, escalating dose study | Radio-opaque markers | Dose of 2 mg bid reduced overall CT time and in caecum/AC and DC (n = 11) | NR |
| 5-HT4 antagonist107 | 20 mg po qd × 10 days | 12 IBS-D (6 F, 6 M) | DB, PC crossover study | Breath hydrogen test | Accelerated orocaecal transit | NR |
| Other agents | ||||||
| Clonidine (α2-adrenergic agonist)108 | 0.05, 0.1 or 0.2 mg/day × 4 weeks | 40 IBS-D (31 F, 9 M) | DB, PC, parallel group dose-ranging study | Scintigraphy | No effect on GE, small intestinal transit or CT | NR |
| VSL#3 (probiotic)109 | Oral dose bid × 4–8 weeks | 48 IBS with bloating (16 IBS-C, 20 IBS-D, 12 IBS-A; 21 F, 27 M) | DB, PC, parallel group study | Scintigraphy | Slowed CT | NR |
| Octreotide110 | Single 50 μg subcutaneous injection | 12 IBS with diarrhoea (9 F, 3 M) | DB, randomised 2 session study 1 week apart | Lactulose hydrogen breath test | Prolonged mouth to caecum transit time | NR |
AC, ascending colon; bid, twice daily; CT, colon transit; DB, double-blind; DC, descending colon; F, female; GE, gastric emptying; IBS, irritable bowel syndrome; IBS-C, constipation-predominant irritable bowel syndrome; IBS-D, diarrhoea-predominant irritable bowel syndrome; M, male; NR, data not reported; NS, not significant; PC, placebo-controlled; po, orally; qd, four times a day; qhs; 4 hourly; SB, single-blind; tid, three times a day.